PROJECT SUMMARY In the United States, COPD ranks third in causes of mortality with 100,000 deaths annually. An estimated 15 million people had health care provider diagnosed COPD in 2010, and an estimated 12 million potential cases remain undiagnosed. Emphysema is a progressive, incurable form of COPD that causes significant morbidity and mortality. Emphysema is characterized by the loss of lung elasticity, reduced expiratory flow and hyperinflation. Lung volume reduction surgery is known to be an effective option for patients with moderate- severe emphysema, but few patients qualify due to the invasiveness of the procedure. Minimally invasive endobronchial lung volume reduction using one-way valves has recently been developed to address this unmet need and was approved by the FDA as recently as 2018. This proposal will validate a new, next generation Super Valve for endobronchial lung volume reduction that will broaden the use of this approach to treat patients with emphysema. Our innovation exploits the anatomy of the lobar segments of the lungs to achieve lung volume reduction using a single site instead of 3-6 sites required by the current methods. This, in turn, will lead to a faster and more efficient procedure, reducing overall surgical time and costs. This project will be completed in several sequential stages. For Phase I we will finalize concept selection for the valve design and demonstrate proof of technical concept on the bench and in acute preclinical studies that our Super Valve can be deployed in lobar airways and that it can withstand physiological stresses. In Phase II of this proposal we mature the Valve design for chronic implantation by developing features that ensure an air-tight seal and prevent migration in the setting of normal respiration and cough. We will then verify and validate a human grade valve system to FDA standards and ensure it is safe for implantation over the lifetime of the patient. The safety and durability of our valves will be demonstrated in chronic preclinical studies. The results obtained in Phase II will be used to support pre-IDE meeting with the FDA.